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Garcia-Cardena, G., R. Fan, et al. (1996). "Endothelial nitric oxide synthase is regulated by tyrosine phosphoryiation and interacts with caveolin-l." Journal of Biological Chemistry 27 l(M): 27 237 -40. Gardiner, S. M., A. M. Compton, et al. (1990). "Control of regional blood flow by endothelium-derivednitricoxide.''@15(5):486-92. Gardner, R. M., R. O. Crapo, et al. (199r). 1E""ffiion of accuracy and reproducibility of peak flowmeters at 1,400 m." @! 101(4): 948-52' Garenne, M., C. Ronsmans, et al. (L992YThe magnitude of mortality from acute respiratory i"i".ir""r i;;ilHt;" under 5 years in devJoping countries." World Health Slatistics .?f a\- I C)n rll 45(2-3):180-91 Garthwaite,J.(1991@dcell-cellsignallinginthenerVoussystem.'' Trends in Neurosciences l4(2):60-7 ' Garthwaite, J., S. ft[*t-rr, rt al. (1988). "Endothelium-derived relaxing factor release on activation of NMDA receptors suggests role as intercellular messenger in the brain'" Nature 336(6197): 385-8. Gaston, B., J. M. Drazen, et al. (1994). "Relaxation of human bronchial smooth muscle by Snitrosothiols in vitro." Joumal of Pharmacology & Experimental TheraPeutics 268(2): 978-84. Gaston, B., J. M. Drazen, et al. (Lgg4). "The biology of nitrogen oxides in the airways"' inel49(2Pt 1):538-51. Gaston,B.,J.rr,r.ffihebiologyofnitrogen^"i1qT.l"':xI: [Review] [205 refs]." Feb 149(2 Pt 1): 538-51. Gaston, B., J. Reilly, et al. (1993). "Endogenous nitrogen oxides and bronchodilator snitrosothiot, in t oman airways." ProcJedings of the National Academy of Sciences of the United States of America N(23): 10957-61' Gaston,B.,s.s"--,,"tul.(1998l''BronchodilatorS-nitrosothioldeficiencyinasthmatic respiratory failure." Lancet 351(9I l2): l3I7-9' Gauderman, w. J. (2006). 'Air pollution and children--an unhealthy mix." New England Journal of Medicine 355(l): 78-9. CauOerrnan, W. J., ffio-tu, et al. (2007), "Effect of exposure to traffic on lung development from 10 to 18 years of age: a cohort study." Lancet 369(9561): 571-7 ' Gaultier, C., M. g. Fletcher, ei al. (1995). "Rlspiratory function measurements in infants: measurement conditions. Working 6roup of tn" Eutopean Respiratory Society and the American Thoracic Society." European Respiratory Journal 8(6): 1057-66' Gauvreau, G. M., J. M. I-ee, .t ui. (ZOffi*t"^tO numbers of both airway basophils and mast cells in sputum after allergen inhalation challenge of atoglc^asthmatics' icine 161(5):1473-8. Gelb, A of spiromel? nitric oxide to 11lilhded predict exacerbations in treated asthmatics." @! 129(6): L492-9. Georas, S. N., M. C. Liu, et al. (1992). "Altered adhesion molecule expression and endothelial cell activation accompany the recruitment of human granulocytes to the ]ung after segmental antigen challenge." Biology 7(3):261-9. Georges, G., B. B. Bartelson, et al. (1999). "Circadian variation in exhaled nitric oxide in nocturnal asthma." Journal of Asthma 36(5): 467-73' Gerlach, H., R. Rossaint, et al. (199t). "Time-course and dose-response of nitric oxide inhalation for systemic oxygenation and pulmonary hypertension in.patients with adult respiratory distress syndrome." European Journal of Clinical Investigation 23(8): 499' 502. Gerlach, H., R. Rossaint, et al. (1994). "Autoinhalation of nitric oxide after endogenous synrhesi s in nasopharynx. I see comment]. " La]lcet.F€u. 26(3 43 (8896)) : 5 I 8-9' 297
Gershman, N. H., H. Liu, et al. (1999). "Fractional analysis of sequential induced sputum samples during sputum induction: evidence that different lung compartments are sampled at different time points." Journal of Allergy & Clinical Immunology l04QP" I):322-8. Gershman, N. H., H. H. Wong, et al. (1996). "Comparison of two methods of collecting induced sputum in asthmatic subjects." European Respiratory Journal 9(12):2448-53. Ghiro, L., S. Zanconato, et al. (2002). "Effect of montelukast added to inhaled corticosteroids on fractional exhaled nitric oxide in asthmatic children." European Respiratory Journal 20(3): 6304. Giannini, D., A. Di Franco, et al. (2000). "Analysis of induced sputum before and after withdrawal of treatment with inhaled corticosteroids in asthmatic patients." Clinical & Experimental Allergy 30(12): 1777 -84. Gibson, P.G., J. L. Simpson, et al. (2003). "Relationship between induced sputum eosinophils and the clinical pattern of childhood asthma." Thorax 58(2): 116-21. Giel, C., M. Kleinfeld, et al. (1957). "Health hazards associated with inert-gas-shielded metal arc welding." A M. A. Archives of Industrial Health. 15(1): 27-3L Gill, M., S. Walker, et al. (2005). "Exhaled nitric oxide levels during acute asthma exacerbation. " Academic Emergency Medicine l2(7): 57 9 -86. Gilliland, F. D., W. J. GauderTnan, et al. (2002). "Effects of glutathione-S-transferase Ml, T1, and Pl on childhood lung function growth." American Journal of Respiratory & Critical Care Medicine 166(5): 710-6. Gilliland, F. D., Y. F. Li, et al. (20M). "Effect of glutathione-S-transferase Ml and Pl genotypes on xenobiotic enhancement of allergic responses: randomised, placebocontrolled crossover study." Lancet 363(9403): IL9-25. Gilliland, F. D., E. B. Rappaport, et al. (2002). "Effects of glutathione S-transferase Pl, Ml, and T1 on acute respiratory illness in school children." American Journal of Respiratory & Critical Care Medicine 166(3): 346-5L. Gilmour, M. I. (1995). "Interaction of air pollutants and pulmonary allergic responses in experimental animals. " Toxicolog), 105(2-3): 335-42. GINA (1995). Global initiative for asthma: global strategy for asthma management and prevention. B. M. Sheffer AL, Bousquet J. Bethesda, USA, National Institutes of Health: NIH publication No 93-3659. GINA QOf.D. Global Initiative for Asthma 200.2. Update from: Global Statergy for Asthma Management and Prevention. DItrIS publication number (NIH) 02-3659. Bethesda, Md., National Institutes of Health. GINA (2004). Global Burden of Asthma. Developed for Global Initiative for Asthma. D. F. Matthew Masoli, Shaun Holt & Richard Beasley. World Health Organisation: l-119. GINA (2005). Global Initiative for Asthma. Pocket guide for asthma management and prevention in children. A pocket guide for physicians and nurses. World Health Organisation: l-34. Giraud, G. D., B. Nejadnik, et al. (1998). "Physical characteristics and gas composition of nasal air affect nasal nitric oxide release." Respiration Physiology 114(3): 285-96. Girgis, R. E., M. K. Gugnani, et al. (2002). "Partitioning of alveolar and conducting airway nitric oxide in scleroderma lung disease." American Journal of Respiratory & Critical Care Medicine 165(12): 1587-91. Godden, J. W., S. Turley, et al. (1991). "The 2.3 angstrom X-ray structure of nitrite reductase from Achromobacter cycloclastes." Sc[ence 253(5018): 438-42. Godfrey, S., C. Springer, et al. (1999). "Cut-off points defining normal and asthmatic bronchial reactivity to exercise and inhalation challenges in children and young adults." European Respiratory Journal 14(3): 659-68. Goggins, M. G., S. A. Shah, et al. (2001). "Increased urinary nitrite, a marker of nitric oxide, in active inflammatory bowel disease." Mediators of Inflammation 10(2): 69-73.
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UNIVERSITV OF AUCKI'AND Abstract -
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There was no significant difference
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This is Dedicated: Dedication To th
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New Zealand The Paediatric Departme
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Contents Abstract ........tr Dedica
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6.5.4 The subjects............... .
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XIV
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List of Figures Figure l.l: Top l0
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List of Abbreviations ABPA allergic
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LADA N*N* dimethyl L-arginine LFA1
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t}ryem(eNoS)Typeltrendothelialnifti
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area, some of it has been expanded
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In addition, both of these groups a
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studies conducted throughout the Un
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Video clips of infants with a varie
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the Paediatric Society of New 7*ala
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inhaled anti-cholinergic agents and
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ecommended to monitor asthma at hom
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improvement to 70Vo PEF would have
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Furthermore, investigators have als
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poorer predictor of a diagnosis of
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Bronsky et al. 1998), and a long-te
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SIGN guideline (SIGN 2005) stated "
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In brief, the human airway can be d
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The ability to biopsy has led to st
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small proportion of cells recovered
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methodology of sputum induction and
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et al. 1999; Giannini, Di Franco et
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over a six month treatment prograrn
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There are other studies suggesting
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So is induced sputum in adults and
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asymptomatic patients independent o
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onchial hyper-responsiveness (Reich
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led to research which looked for le
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analyser machines. This thesis pres
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The pollution of the 'great smog of
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adults greater than 65 years (Ostro
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levels compared to those children l
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More recently 'Air Quality Indexes'
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acetylcholine. These were known to
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cyclase does not produce significan
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Garthwaite l99l), and the non adren
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significant complication, this trea
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locus for the enzyme is a susceptib
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NO synthesis and in so doing blocke
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3.1 Chapter 3: The synthesis, react
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BHa = tetrahyrobiopterin, FAD = fla
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(Knowles, McWeeny et al. 1974) and
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more potent at low oxygen tensions
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toxic products such as isoprostanes
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Figure 3.3: The nitric oxide syntha
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providing NO as a neurotransmitter
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The enzyme of this second pathway -
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inappropriate production from comme
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Nicotinamide adenosine dinucleotide
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enzyme and are competitively revers
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4.1 Introduction Chapter 4: Methods
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4.4 Nitrite and nitrate The measure
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insensitive (Braker and Mossman 197
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A group of instruments have been de
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The original group demonstrated tha
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equired it. For example, there was
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helium for 30 minutes to remove Oz.
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(Postlethwait and Bidani 1990; Post
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is set at 5ppm (AIHA 1966) based on
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5.1 Chapter 5: Methodological asses
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wanted to compare the patterns of e
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in different colours that became th
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an advisor for this work and main s
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Delay time: the time between turnin
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led to an increased water content t
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Chapter 6: Methodological studies o
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pulmonary circulation appeared to c
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al found levels of 10.3ppb compared
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Authors and Pap€r Sublect numbers
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only those measured by mouth or low
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6. Check that the pens work. Fill w
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keys but it is currently in the mid
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Calibration pressures: the test por
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T-piece: tO The first figure shows
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the rotameter. Tracings of each par
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Figure 6.6: Mean exhaled NO levels
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NO and COz results from single exha
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6.6.4 (iii) Comparison of exhaled n
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Figure 6.11b: COz levels at peak NO
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I also considered whether the diffe
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the direct to the indirect method l
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need for methodological experiments
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The exhalations were carried out in
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Figure 7.2: Example of the tracing
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7.4.4 Results There was an increase
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Table 7.3: NO, COz and duration of
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The second set of exhalations invol
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Figure 7.6: Photographs of the chan
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Table 7.5: Exhaled NO results with
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the NO concentrations taken pre and
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Figure 7.10: Hyperbolic relationshi
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pressure over the likely range enco
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subjects with respiratory disease,
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8.1 Chapter 8: Exhaled nitric oxide
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standard error of the mean (SEM), s
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T-piece sampling system to analyser
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Figure 8.2a: Comparison of peak exh
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if yes who? if yes who? if yes who?
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There are limitations with regard t
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significantly between research grou
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controls. Kharitinov et al reported
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direct method in asthmatic children
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Figure 8.4a: The eftect of commenci
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had last used her p2 agonist inhale
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higher level of exhaled NO at 4.9pp
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9.1 Introduction Chapter 9: Exhaled
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For the oral measurements options i
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Table 9.1: The recommended standard
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taken from the available literature
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compartment correlated with the ser
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measurement with variable expirator
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to settle. We may have been measuri
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9.5 Off-line measurement NO determi
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(Hyde, Geigel et al. 1997; Tsoukias
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9.6 Nasal nitric oxide measurement
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measured over two 24 hour periods,
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women who coincidently experienced
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While these cross-sectional and the
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symptoms. Steroid response was sign
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'difficult asthma' also had higher
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season and then reduced down to bas
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of cross sectional studies with a t
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Ciabattoni et al. 2004; Petersen, A
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FEV9.5, symptom score and airways r
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Indomethacin - This medication alte
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89Vo for PCD, and above that exclud
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This low NO occurs despite higher t
Page 269 and 270: patients were followed through one
Page 271 and 272: differences noted based on filter,
Page 273 and 274: 9.L6 Nitric oxide levels in exercis
Page 275 and 276: another study of 111 school childre
Page 277 and 278: Almost all studies used sedation, w
Page 279 and 280: peak exhaled NO production in the f
Page 281 and 282: flow and to minimize nasal contamin
Page 283 and 284: ecruit blood vessels in the lung. S
Page 285 and 286: Chapter 10: Reflections The outcome
Page 287 and 288: and I enrolled 52 asthmatic childre
Page 289 and 290: Edwards EA, Douglas C, Broome S, Je
Page 291 and 292: o Cass Byrnes & Nicky Holt. "Drugs
Page 293 and 294: o Byrnes CA. Paediatric fibreoptic
Page 295 and 296: Appendix 2: Questionnaire for enrol
Page 297 and 298: Al-Ali, M. K. and P. H. Howarth (20
Page 299 and 300: Archer, S. L., P. J. Shultz, et al.
Page 301 and 302: Baraldi, E., N. M. Azzolin, et al.
Page 303 and 304: Belda, J., P. Hussack, et al. (2001
Page 305 and 306: Bongers, T. and B. R. ODriscoll (20
Page 307 and 308: Brown, G. C. and C. E. Cooper (1994
Page 309 and 310: Castro-Rodriguez, J. A., C. J. Holb
Page 311 and 312: Cockcroft, D. W., D. N. Killian, et
Page 313 and 314: de Blic, J., V. Marchac, et al. (20
Page 315 and 316: Donaldson, S. H., W. D. Bennett, et
Page 317 and 318: Emi-Miwa, M., A. Okitani, et al. (1
Page 319: Frey, U., J. Stocks, et al. (2000).
Page 323 and 324: Grasemann, H., E. Michler, et al. (
Page 325 and 326: Hashimoto, T., K. Minoguchi, et al.
Page 327 and 328: Holgate, S. T., D. E. Davies, et al
Page 329 and 330: Iriso, R., P. M. Mudido, et al. (20
Page 331 and 332: Jones, A. W., M. Fransson, et al. (
Page 333 and 334: Kercsmar, C. M. (2006). Wheezing in
Page 335 and 336: Kleinert, H., T. Wallerath, et al.
Page 337 and 338: Lamblin, C., P. Gosset, et al. (199
Page 339 and 340: Li, X. and J. W. Wilson (1997). "In
Page 341 and 342: Lymar, S. V. and J. K. Hurst (1996)
Page 343 and 344: Massaro, A. F., S. Mehta, et al. (1
Page 345 and 346: Miyabara, Y., R. Yanagisawa, et al.
Page 347 and 348: contribute to impaired endothelium-
Page 349 and 350: ODell, T. J., R. D. Hawkins, et al.
Page 351 and 352: Panza, J. A., C. E. Garcia, et al.
Page 353 and 354: Peters, S. P. (2006). "Safety of in
Page 355 and 356: Prieto, L., L. Bruno, et al. (2003)
Page 357 and 358: Ribbons, K. A., X. J. Zhang, et al.
Page 359 and 360: Sacco, O., R. Sale, et al. (2003).
Page 361 and 362: Sessa, W. C., K. Pritchard, et al.
Page 363 and 364: Silvestri, M., F. Sabatini, et al.
Page 365 and 366: Stamler, J. S. (1994). "Redox signa
Page 367 and 368: Stuehr, D. J., N. S. Kwon, et al. (
Page 369 and 370: Tierney, W. M., J. F. Roesner, et a
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Upchurch, G. R., G. N. Welch, et al
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Wadsworth, R., E. Stankevicius, et
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Williams, O., R. Y. Bhat, et al. (2
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Yates, D. H., S. A. Kharitonov, et
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